In chemical, biochemical, biological and pharmaceutical fundamental and applied research automated high-throughput assays are frequently applied to gain knowledge about chemical compounds, biological samples, clinical samples and processes related to the assayed compounds and samples. For example, in drug discovery processes, a wide variety of high-throughput experiments can be carried out to explore the biological activity of molecules. Particularly, in cases where there exists only little knowledge about the structure-activity relation between a biological target and compounds interacting with the target, high-throughput screening (HTS) is typically applied.
Usually in HTS-experiments large numbers of compound samples are assayed wherein the samples are frequently used in small amounts, for example in the range of few microliters, and handled in microplates. Widespread standards defining microplates of about 127.76 mm length, 85.48 mm width and various heights comprising 96, 384 or 1536 wells have been developed by the Society for Biomolecular Sciences (SBS) and have been approved by the American National Standards Institute (ANSI) [see Society for Biomolecular Sciences. ANSI/SBS 1-2004: Microplates—Footprint Dimensions, ANSI/SBS 2-2004: Microplates—Height Dimensions, ANSI/SBS 3-2004: Microplates—Bottom Outside Flange Dimensions and ANSI/SBS 4-2004: Microplates—Well Positions. http://www.sbsonline.org: Society for Biomolecular Sciences, 2004.]. Using such microplates, each sample is held in a fixed and well-defined position in the plate such that automated handling of the samples is possible. As an alternative to microplates having wells for accommodating the samples, standard compliant microplates having removable microtubes instead of wells are also used. Such microtubes can be advantageous since they can be sealed and thereby easily transferred between several microplates in a sealed state. Particularly, when the samples additionally are held frozen inside the microtubes, they can efficiently be transferred from one microplate to another microplate without impairing the frozen state of the samples.
For having compound samples ready when needed for an HTS-experiment specific libraries are set up wherein large numbers of samples, i.e. millions of compound samples, can be stored in accordingly large amounts of microplates. Typically, the microplates comprising the compounds are thereby cooled, for example to −20° C., for ensuring long term stability and stored in a humidity controlled room. The microplates can be positioned in racks with drawers wherein each drawer, each microplate as well as each well or microtube can be encoded. The compounds needed can be gathered automatically by a robot being as well arranged inside the cooled, humidity controlled room. For example, when using microplates with microtubes, the robot can be moved to a predefined drawer, open the drawer and access a source microplate holding the microtube with a selected compound sample. Then, the robot removes the microtube from the source microplate and inserts it into a delivery microplate. This step can for example be efficiently performed by pushing the microtube through the source microplate into the delivery microplate. Similarly, the robot gathers the next selected compound for the same HTS-experiment of its corresponding source microplate and puts it into the same delivery microplate. At the end the robot provides a set of delivery microplates holding the compounds selected for a certain HTS-experiment. Since typically a number of compounds with specific properties are needed in HTS-experiments, the robot can efficiently gather selected compounds when all compounds are logically ordered in sample libraries with racks as described above.
Such a sample library having racks with drawers and a gathering robot, both being arranged in a humidity controlled room cooled to for example −20° C., is for example described in EP 0 904 841 B1 wherein single microtubes held in a source microplate are pushed into a delivery microplate in a separate transfer station, such that the source microplate has to be relocated to the transfer station and back to the drawer.
High-throughput assays as described above are as well used for clinical studies, wherein samples comprising for example blood and serum are used instead of compounds. Said samples can as well be handled in microplates and reasonably, libraries with such samples are set up as well. For the long term storage of such samples it is not sufficient to cool the samples down to a temperature range as described above but they need to be cooled down to a lower temperature range, as for example to a temperature of about −80° C. However, cooling of a complete humidity controlled room for storing microplates holding the samples as described above to said temperatures is not economically feasible. Further, at said temperatures, standard handling devices, such as for example robots, usually do not work properly. Therefore, particularly for long term storage of microplates, special boxes are known in the art. By using such boxes and thereby reducing the space needed to be cooled down to said temperatures a comparably economic storage of microplates is possible.
For example, such a box is shown in U.S. Pat. No. 6,688,123, wherein a carousel having vertical racks and an interchange mechanism are arranged in the interior of the box. The microplates are arranged on the vertical racks such that the interchange mechanism is capable of shoving an interchange tray underneath the microplate and thereby removing the microplate from the rack. Since the interchange tray has to be shoved underneath the microplate, the microplates have to be spaced apart from each other. Additionally, the interchange mechanism has to be arranged inside the box as well. Thus, the interior space of the box having to be cooled is comparably large. Further, the interchange mechanism has to be arranged to work at the mentioned temperature ranges which can reduce its configuration possibilities. Still further, the prevention of icing while handling a microplate is a difficult task which can reduce the handling efficiency or which can even impair the samples stored in the microplate.
Therefore there is a need for a device allowing a compact efficient economic storage of microplates and the samples therein as well as for a device and a method allowing an efficient economic handling of microplates and the samples therein.